https://repositorio.ufms.br/handle/123456789/65 2026-04-15T04:06:08Z https://repositorio.ufms.br/handle/123456789/14206 Título: CRISTAIS MULTICOMPONENTES FARMACÊUTICOS DE CARVEDILOL COMO ESTRATÉGIA PARA MELHORAR A ESTABILIDADE TÉRMICA Abstract: Understanding and manipulating the physicochemical properties of the solid state of Active Pharmaceutical Ingredients (APIs) are crucial for the development of new drugs. Among the relevant properties of a drug, solubility, intrinsic dissolution, permeability, and bioavailability stand out. In this context, crystal engineering of pharmaceutical compounds emerges as an essential tool. It enables rational planning and the development of new solid forms through the strategic use of supramolecular synthons. Carvedilol (CVD), an antihypertensive drug belonging to the beta-blocker class, is used to treat cardiovascular diseases. This API falls into Class II of the Biopharmaceutical Classification System (BCS), exhibiting low solubility and high permeability. Based on a literature search and a detailed analysis of molecular interaction, crystals were successfully obtained using the following acids: nitric, maleic, benzoic, and p-toluenesulfonic. The salts were prepared via evaporative crystallization methods, and the resulting phases were characterized using single-crystal X-ray diffraction and thermal analysis, complemented by powder X-ray diffraction data. Four Carvedilol salts were obtained: Carvedilol Nitrate (CVD-NO3), Carvedilol Maleate (CVD-MAL), Carvedilol Benzoate (CVD-BZN), and Carvedilol Tosylate (CVD-TOS). The crystal structures of the nitrate and maleate salts are isostructural. Both crystallize in the triclinic space group P1 ̅ and present as hydrates due to the incorporation of water molecules into the crystal lattice. CVD-TOS also presents as a hydrate, crystallizing in the Fdd2 space group. In contrast, CVD-BZN crystallizes in the triclinic space group P1 ̅ with an anhydrous structure. Thermal analyses confirm that the CVD-BZN salt is the most thermally stable, with degradation occurring at 160 ºC. For CVD-MAL, dehydration occurs at 75.6 ºC and degradation at 171 ºC, indicating lower stability. Therefore, the results presented in this work provide important and innovative scientific contributions, particularly concerning the possibility of improving the biopharmaceutical properties of the studied APIs. Tipo: Tese 2025-01-01T00:00:00Z https://repositorio.ufms.br/handle/123456789/14198 Título: DESENVOLVIMENTO DE MÉTODO COLORIMÉTRICO PARA DETERMINAÇÃO DO AMINOÁCIDO 5-HIDROXITRIPTOFANO EM FÁRMACOS Abstract: L-5-hydroxytryptophan (5-HTP) is an aromatic amino acid produced in the human body from L-tryptophan, derived from dietary proteins. However, supplementation with L tryptophan does not significantly increase 5-HTP levels, which is mainly obtained from the seeds of Griffonia simplicifolia Baill. and widely used as a dietary supplement. Due to its therapeutic application in the treatment of conditions such as depression, fibromyalgia, insomnia, obesity, and chronic headaches, the accurate determination of 5 HTP is essential to ensure the quality of pharmaceutical and dietary supplement products. In this work, a simple and low-cost colorimetric method was developed for the determination of 5-HTP, based on the reaction with the Folin–Ciocalteu reagent and the analysis of digital images acquired using a smartphone. The reactions were carried out in microwells of a miniaturized device fabricated by 3D printing, with image acquisition performed under controlled lighting, positioning, and distance conditions. The color intensity of the reaction product was evaluated using the RGB color system with the aid of the Colorimeter application. Optimization studies involving reaction volume, reaction time and reagent concentration were conducted, establishing the following optimal conditions: total volume of 40 µL (24 µL of 5-HTP solution, 8 µL of 0.10 mol·L⁻¹ Folin Ciocalteu reagent, and 8 µL of 7.5% Na₂CO₃ solution) and a reaction time of 20 minutes. An analytical curve was constructed over the concentration range from 1.5 to 12.0 mg·L⁻¹, with a determination coefficient of 0.9948, indicating satisfactory linearity and RSD values below 13 %. The limits of detection (LOD) and quantification (LOQ) achieved were 0.346 mg·L⁻¹ and 1.155 mg·L⁻¹, respectively. In the interference study, common inorganic ions did not significantly affect the colorimetric signal of 5-HTP, whereas reducing species, such as ascorbic acid and catecholamines, promoted pronounced interference. The proposed colorimetric method was applied to the quantification of 5 HTP in pharmaceutical samples. Method accuracy was verified by comparison with UV Vis spectrophotometry, showing good agreement between the results, with relative errors below 10%. All analyzed pharmaceutical samples complied with the specifications established by the Brazilian Pharmacopoeia for active ingredient content. The results indicate that the proposed method is precise, reliable, and presents potential for application in routine analyses and quality control of commercial 5-HTP supplements. Tipo: Dissertação 2025-01-01T00:00:00Z https://repositorio.ufms.br/handle/123456789/12840 Título: Estudo de metabólitos secundários das folhas de Galianthe thalictroides (Rubiaceae) Abstract: The investigation of natural products remains an essential strategy for the discovery of new bioactive molecules, particularly within the context of Brazilian biodiversity. In this scenario, the present study focused on the phytochemical investigation of the leaves of Galianthe thalictroides (K. Schum.) E. L. Cabral (Rubiaceae), a shrubby species with restricted distribution in South America and traditionally used in folk medicine. The ethanolic extract of the leaves was subjected to systematic extraction, fractionation, and purification procedures, which resulted in the isolation of three β-carboline alkaloids. The structural characterization of these substances was carried out through integrated techniques of one- and two-dimensional NMR, UV-Vis and infrared spectroscopy, as well as high-resolution mass spectrometry (HR-ESI-MS). Among the isolated compounds, two revealed an unprecedented architecture, formed by the association of monoterpene portions with flavan-3-ol (epicatechin) units, constituting a new class of β-carboline–flavonoid hybrid alkaloids. This structural originality confers uniqueness to the species and significantly expands the knowledge about the chemical diversity of the Rubiaceae family. In addition to their novelty, such molecules present potential for future bioactivity studies, given the previously reported cytotoxic and antimicrobial activities for alkaloids of this class. The results obtained confirm the relevance of G. thalictroides as a promising source of structurally complex and biologically relevant secondary metabolites, reinforcing the importance of valuing the flora of the Brazilian Cerrado as a chemical and biotechnological heritage. Tipo: Dissertação 2025-01-01T00:00:00Z https://repositorio.ufms.br/handle/123456789/12766 Título: Preparação e caracterização de suporte híbrido para imobilização de penicilina G acilase Abstract: Enzymatic immobilization on organic-inorganic hybrid supports emerges as a promising strategy to optimize the production of 6-aminopenicillanic acid (6-APA), combining the stability of silica with the sustainability of agro-industrial waste such as cumbaru endocarp. This study aimed to develop and characterize a hybrid support based on silica and cumbaru endocarp (Dipteryx alata Vogel) for the immobilization of the enzyme penicillin G acylase (PGA), targeting the production of (6-APA) through the enzymatic hydrolysis of penicillin G. Hybrid matrices with different percentages of cumbaru endocarp (1%, 1.5%, and 2%) and silica were prepared by the sol-gel method. Matrices with silica and 2% cumbaru endocarp, previously treated with dioxane and sodium periodate, were also prepared. Subsequently, all prepared hybrid supports were activated with glutaraldehyde and epichlorohydrin. The characterization of the prepared supports was carried out using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). SEM and FTIR analyses confirmed the successful formation of the hybrid support, revealing a porous structure and the presence of essential functional groups for enzyme immobilization. The TGA results demonstrated that the hybrid support activated with glutaraldehyde exhibited higher thermal stability, with a mass loss of only 16.3% up to 700°C, compared to the other prepared supports, highlighting its robustness for industrial applications. After characterization, the hybrid support prepared with silica and 2% cumbaru endocarp activated with glutaraldehyde was selected to carry out the immobilization of penicillin G acylase (PGA) by the covalent binding method. Subsequently, the enzymatic activity of the free and immobilized enzyme was determined, along with the immobilization yield (29%). Despite the relatively low immobilization yield obtained, the developed hybrid support, with the necessary adjustments, shows promising potential for biotechnological applications, standing out as a sustainable alternative for industrial processes based on biocatalysis. Keywords: Enzyme immobilization, penicillin G acylase, hybrid support, cumbaru endocarp, 6-aminopenicillanic acid. Tipo: Dissertação 2025-01-01T00:00:00Z